Preparation for medicinal use



Patented May 2, 1939 PREPARATION sou MEDICINAL USE Bernard L. Wyatt and Harry E. Thompson, Tucson, Aria, assignors, by mesne assignments, to Armour and Company, Chicago, 111., a corporation of Illinois No Drawing. Application May 24, 1937,

Seria l No.'144,544=

' 12 Claims. (01. 167-58) This invention relates to a preparation for medicinal use and more particularly to a prepara tion. of this character for the treatment of arthritlo and fibrositic patients. Research has shown in casesof arthritisand fibrositis that an analgesia was produced byv an intercurrent jaundice with resultant relief from pain and/or a diminution of joint swelling where k the patients under observation incurred jaundice uyduringthe course of arthritis of fibrositis.

The importance of this observation has led to experiment in the production of jaundice in such patients with an object of the eventual use of jaundice as a therapeutic agent.

J aundice (icterus) is due to the presence of the coloring matter'of the bile or other pigments in the blood and tissues in certain amounts and is caused either by obstruction of the biliary pas sages, the action ofchemical or bacterial poisons upon the liver, the excessiveflestruction of red blood cells, etc.; or may be induced as a therapeutic measure by repeated injections of bile or other pigments in combination with bile acids or alkali metal salts thereof.

Bile contains components which may be divided into five groups: (1)- inorganic salts and sodium carbonate; (2) bile pigments such as bilirubin,'

(hyperbilirubinemia) may be inducedby'repeated intravenous injections of the preparation hereinafter described with resultant analgesic and a remedial eflects upon casesv of arthritis and ilbrositis.-

Bile pigments,'such as bilirubin, biliverdin, and biliprasin or their derivatives are combined either chemically or otherwise with bile acids, including 4| those occurring naturally onsynthetically such as cholic, glycocholic, taurocholic, dehydrocholic, mono, di and triketocholic; or mixtures 01 these acids or the metal salts of; such acids. These salts include the group of sodium, potassium; 5 magnesium, and calcium or other salts of metals. The combination or these ingredients may take place alone or, in an alkaline solution using the carbonates or. hydroxides of potassium or other alkali, the alkalinity being of wide range .5 as to pH. The combination mayalso be effected maintained with 1' alone or in an acid solution using organic or inorganic acids, the acidity being of wide-range as to pl-I and the acid selection dependent upon cir-. cumstances. Bilirubin at the present time is believed to be thebile pigment for most eiIective 5 use in connection with this'invention.

The process of preparation involves filtration, precipitation or similar procedure to facilitate a chemical or other combination or mixture of bile pigment with bile acids or their salts either in 10 solution or as a dry substance.

A specific example of preparation is as follows:

Using asbile pigment, bili-rubin, two-tenths to one gram is dissolved in fromltl to 300 cc., onetenth normal solution of sodium carbonate, the 1:5

mixture being heated for a short time under centigradeboiling point. The resultant solution or mixture is filtered and the pH thereof determined and adjusted. To this is added a solution of bile acid such as the sodium salt of dehydro- 20 cholic acid in the ratio of one-half to ten cc. of the sodium salt in a 20% finished solution or its equivalent amount in dry form.

, This is done under conditions which or eliminate oxidative or reductive changes in the bilirubin. The bile pigment is tested for color value by the Ernst-Fiirster or Peterman-Cooley tests, a 90% tinctorial value having been found desirable. An inorganic acid, for this example, hydrochloric, may be added to the solution as a means of pH adjustment. A pH of 9.4 has beendetermined as suitable, but such pH is not definite and depends upon conditions pertaining to the preparation of the product.

It the product is desired in dry form, it may Y be so prepared by evaporation or other means.

' Bile pigments are amphoteric and essentially non-toxic and may be used for human dosage;

result when either is administered singly.

It is obvious .that if biliverdin is used, the biliverdinate is formed in the first step, while in the intermediate steps substitution oi other bileacids or their salts will give other results, as for instance if taurocholic acid salts be used, the result is a potassium or sodium taurocholate, a similar substitution being the metal salts oi.' ketocholic acids.

Tests of this preparation upon rabbits has determined that jaundice may be induced and ated intravenous injections of from 10 to 20 mgs. per kilo of body weight or the rabbits. A singlefatal dose was determined amass:

to be 175 to 200 mgs. per kilo of body weight. ing a bile pigment, a salt 01 a bile acid, and an Tests upon patients with intravenous injection 01 bile or other body fluid pigments alone have given no beneficial eifect in arthritis or fibrositis and only slight degrees of jaundice were induced. By dosage suflicient to maintain a bile pigment at an elevated level with the preparation described herein, patients secured reliei irompain within a short time after treatment and(or diminution or joint or other swelling occurred. These results were due to the induced jaundice caused by, the repeated injections of our preparation.

The use of our preparation has also given an inhibitory efl'ect in streptococci diseases.

We claim: 1. A preparation for medicinal use for the treatment of arthritis and fibrositis comprising a bile pigment and one 0! the class consisting of bile acids and salts of bile acids.

2. A preparation for medicinal use for the treatment of arthritis and ilbrositis comprising a bile pigment and one of the class consisting of bile acids and salts'oi bile acids and an alkali.

3. A preparation for intravenous use comprising a bile pigment, a salt of a bile acid, and an alkali combined in solution. V

- 4. A preparation for intravenous use comprising a bile pigment, a salt of a bile acid, and an acid other than said bile acid combined in solution.

5. A preparation for intravenous use comprisorganic acid other than said bile acid combined in solution.

6. A preparation for intravenous use comprising a bile pigment, a salt of a bile acid, and an inorganic acid other than saidbile acid combined in solution. I

7. A preparation for the treatment of arthritis and fibrositis comprising bile pigment, bile acid, and an alkali combined to form an intravenous injection for inducing jaundice or hyperbilirubinemia. v

8. A preparation for the treatment of arthritis and flbrositis comprising bile pigment, bile acid, and an'acid other than said bile acid combined to form an intravenous injection for inducing jaundice or hyperbilirubinemia.

9. A preparation for intravenous use comprising a bile pigment and a bile acid.

10. A preparation for intravenous use comprising a bile pigment and a salt of a bile acid.

11. A preparation for medicinal use for the treatment of arthritis'and fibrositis comprising bilirubin and one of the class consisting of bile acids and salts of bile acids. A

12. A preparation for medicinal. use for the treatment of arthritis and fibrositis comprising bilirubin and one of the class consisting of bile acids and salts of bile acids and an alkali.

- BERNARD L. WYA'I'I.

HARRY E. THOMPSON. 

